Technique for producing a sustained release drug has been developed for various types of drugs to improve patients' compliance along with the advancement of manufacturing techniques. A sustained release drug has many benefits in efficacy and safety such as effectively induced pharmaceutical potency with a reduced number of administrations as well as a decreased incidence of side effect or toxicity owing to lasting drug efficacy compared with a typical immediate release drug.
However, drugs, such as an analgesic, which are also needed to take effect immediately, are also required to take effect immediately after an effective blood concentration is reached rapidly after taking it for rapid pain-relief, or the like. A bilayer tablet including an immediate release part and a sustained release part, a long-acting preparation combining immediate release granules and sustained release granules, and the like have been developed as a preparation that has both fast-acting and long-acting properties.
The long-acting preparation is considered as more excellent preparation when it is more hardly subjected to effect of physiological factors or the like of food and digestive tract and also has smaller intraindividual and/or interindividual variation in order that the blood concentration of a drug is maintained at an appropriate level for an appropriate period of time. To obtain a stable blood concentration, an oral preparation needs to be prepared to have physiological properties in digestive tract, especially not to be subject to pH. A multilayer tablet including an immediate release part and a sustained release part, for example, provides delayed initial elution depending on a tablet making method and/or great variation in the release of a medicinal ingredient depending on pH of eluate. Such phenomena may occur during production using a continuous tableting machine for massproduction, due probably to mixing of a sustained release component into an immediate release part caused by attaching or remaining of a sustained release part within the machine.
A long-acting preparation has been studied to reach an effective blood concentration rapidly after administration and sustain its efficacy for a long period of time for an active analgesic ingredient such as tramadol which is an active ingredient of a solid pharmaceutical preparation of the present invention. A multilayer preparation with a form containing an immediate release phase and a sustained release phase that contains at least one kind of opioid analgesic agent has been disclosed (see Patent Document 1). However, there is no description in Patent Document 1 about either a long-acting preparation that has an excellent release property showing little pH dependency in the initial elution of opioid or a technique for making such preparation.
[Patent Document 1]
Japanese Patent Application Publication No. JP-A-10-251149